[unreadable] The nuclear hormone receptors engender great research interest. The Keystone Meeting on Tissue Selective Nuclear Receptors in 2005 will be unique. It will bring together three research groups impacting human health via the nuclear receptors (NR's): (a) basic scientists, (b) pharmaceutical drug discoverers and (c) clinicians. The meeting will define unmet medical needs for tissue-selective NR drugs, recent advances towards a molecular understanding of tissue-selectivity as a hallmark for improved efficacy and safety, and resources workshops to address and fulfill needs for emerging novel research tools. Many new NR drugs are entering the market for diabetes and obesity, thyroid dysfunction, and congestive heart failure but few display even modest tissue selectivity. There is only scant understanding of the mechanisms of tissue selectivity. Co-activator and co-repressor proteins are thought to contribute, but little is known about how complex temporal patterns of gene expression exist in particular tissues. Pharmaceutical science, on the other hand, has created literally thousands of small molecule modulators of nuclear receptor activity. These compounds can be excellent investigative tools, and can be "abandoned" compounds. We propose to bring together researchers from a broad spectrum of science to present a state-of-the-art understanding of nuclear receptor function at the tissue level. The guiding concept will be to present an overview of therapeutic needs for future receptor drugs, assess the degree to which current drugs achieve these profiles, and then present scientific methodology that can advance mechanistic understanding of receptor-ligand function. The meeting will center upon our understanding of a class of transcription factors whose pharmacology touches some of the most prevalent human diseases [unreadable] [unreadable]